In an exclusive conversation with NunaBio chief executive Joe Hedley, he described a bottleneck he thinks the field keeps mislabelling. Design has outrun construction. Models propose sequences faster than any supplier can physically deliver them, and the constructs that come back rejected are rarely the boring ones.
"The simplest way to frame it is that biology became designable faster than it became manufacturable."
Increasingly, Hedley says, manufacturing rather than biology is the rate-limiting step. He points to independent work reporting synthesis failure rates above 20% even after computational screening, with much of biologically useful sequence space still difficult or impossible to build by conventional routes. These include repeat-rich sequences, high-GC regions, inverted terminal repeats, long poly-A tails and other structurally difficult formats.
"The sequences that fail most often are usually the ones that matter most."
Two curves are now crossing. Computational design is rapidly expanding the sequence space researchers want to test, while gene therapy, mRNA and newer modalities increasingly require formats that conventional manufacturing struggles to produce. That creates a problem conventional market estimates do not fully capture: today's DNA synthesis market largely measures the DNA that can already be ordered and manufactured. It says much less about the latent demand for designs that are never attempted, abandoned, or redesigned because they cannot reliably be built.
Conventional gene synthesis is two processes stacked on top of each other. Short oligonucleotides are built base by base, then stitched into longer constructs and, in most workflows, amplified or cloned into a bacterial host for propagation. Each stage carries its own failure mode. Coupling efficiency limits how long an oligo can run before errors accumulate, repetitive and GC-rich stretches misanneal during assembly, and living cells reject what is toxic or unstable once the construct is inside them. The result is a set of sequence features that fall outside what most suppliers will quote on. NunaBio takes a fundamentally different manufacturing approach. It assembles DNA cell-free from pre-characterised inputs rather than synthesising each construct de-novo and relying on cellular propagation.
"Since every construct is built from the same characterised inputs, sequence complexity does not inherently drive manufacturing cost in the way it does in conventional synthesis."
Complexity stops being the thing the customer pays for. The NunaSynth platform packages this into deployable microfoundries, with the NB-3 system producing linear DNA in roughly 80 minutes per batch from nanogram inputs, producing multi-kilobase sequences including a poly-A tails of over 300 bases. The units are stackable, run in batch or continuous mode, and are small enough to sit inside a CDMO or a partner facility rather than replace one. Digital sequence to manufacturing scale, without cells, in under 7 days.
Which is why Hedley resists the industry's default scoreboard.
"Cost per base measures the economics of the supplier, not whether a customer's science can actually happen reliably."
Take a long poly-A tail. Past a certain length it becomes unstable by conventional routes and may never be delivered at all. No price figure captures a sequence that does not arrive. Complexity and format answer the real question, which is whether the science can happen. Price becomes meaningful only once the answer is yes.
The company has raised approximately £11 million to date, backed by investors including Northstar Ventures, and holds ISO 9001 and 27001 certifications with no recorded non-conformances. It has also received multiple industry awards, including the CPHI Accelerating Innovation Award. Next comes higher throughput and the first international microfoundry deployments, with Australia and the United States among the priority markets, alongside early work applying the platform to difficult therapeutic sequences.
Moving that boundary does not simply take share from the existing synthesis market; it expands the biological design space that can become experimentally useful. Most of the field is still competing on fractions of a cent per base. The frontier that matters is further out, at the line separating sequences that can be made from sequences that cannot. For the scientists who have spent years waiting on DNA that conventional suppliers will not touch, that is the line worth moving.
